Teachable moment in classrooms:

  1. cellular basis of life chapter – concept of one gene, one protein
  2. cellular basis of life chapter – concept of gene mutation leading to protein malfunction
  3. cellular basis of life chapter – mRNA translation is needed for protein synthesis
  4. blood chapter – red blood cells are made in the red bone marrow
  5. blood chapter – the role of globin chains in hemoglobin function

The news item:  Recently the following report appeared:

https://timesnewscity.com/bluebirds-2-8m-gene-therapy-becomes-most-expensive-drug-after-us-approval/

The article states that about 1,500 patients need blood transfusion every 2-5 weeks, and that Zynteglo is a gene therapy.

So, Why Do I Care??

The most severe type of beta-thalassemia causes serious anemia with the symptoms of continuous lethargy, fatigue, tiredness. To fight this, the patients require regular blood transfusions. Those patients expected to live until about the age of 50. in the US there are about 1500-3000 such patients. New treatment approaches give the hope of longer life to those patients.

Plain English, Please!!! First, let’s talk about what beta-thalassemia is. This disorder is caused by the missing beta-globin protein in hemoglobin. The protein is missing because the beta-globin gene has mutations that prevent the mRNA formation for beta-globin. The outcome is that hemoglobin is abnormal, because it is formed only from the alpha-globin proteins. Such abnormal hemoglobin makes cells of the red bone marrow to burst, reducing the production of oxygen transporter red blood cells. The decreased oxygen transport cause anemia, the starvation of cells for oxygen.

Second, let’s talk about how red blood cells are made. The damage of the beta-thalassemia is done in the red bone marrow, where red blood cells are formed. In the red bone marrow the red blood cells move through several stages of production, but those stages are interrupted because the abnormal hemoglobin makes those cells to burst. Imagine a car assembly line where a partially made car moves from one station to the next before the car is completed. If a half-assembled car falls apart because of defective bolts or defective welding, then the entire assembly line (red bone marrow) is paralyzed, and no new car (red blood cells) will come off the line.

Third, let’s talk about how Zynteglo works. The Zynteglo treatment aims to provide the missing beta-globin protein for the red bone marrow. This where gene therapy comes in. Zynteglo uses a genetically-engineered virus to add the normal, unmutated beta-globin genes to the red bone marrow cells. To accomplish that, the red bone marrow is removed from the patient, and infected with the engineered virus. Once the engineered bone marrow cells make the normal hemoglobin, they are infused back into the patient where normal hemoglobin production will continue.  Normal hemoglobin will not burst the red bone marrow cells, so red blood cell production returns to normal, which, in turn leads to normal oxygen transport bringing an end to anemia.